Article
Rationale for testing Tumor Treating Fields (TTFields) in Brain Metastases – the METIS trial
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Authors
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Christian Freyschlag
- Universitätsklinik für Neurochirurgie, Medizinische Universität Innsbruck, Innsbruck, Austria
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Johannes Kerschbaumer
- Universitätsklinik für Neurochirurgie, Innsbruck, Austria
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Daniel Pinggera
- Neurochirurgie Innsbruck, Medizinische Universität Innsbruck, Innsbruck, Austria
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Konstantin Brawanski
- A.ö. Landeskrankenhaus - Universitätskliniken Innsbruck, Tirol Kliniken GmbH, Universitätsklinik für Neurochirurgie, Innsbruck, Austria
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Minesh Mehta
- Miami Cancer Institute, Miami, United States
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Paul Brown
- Mayo Clinic, Rochester, United States
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Vinaj Gondi
- Northwestern Medicine Cancer Center, Warenville, United States
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Claudius Thomé
- A.ö. Landeskrankenhaus - Universitätskliniken Innsbruck, Tirol Kliniken GmbH, Universitätsklinik für Neurochirurgie, Innsbruck, Austria
| Published: | June 9, 2017 |
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Outline
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Objective: Surgical treatment of cerebral metastases aims to achieve a long-lasting local control with a low morbidity. However, local recurrence occurs in up to 50 – 70% of surgically treated metastases, if not combined with an adjuvant radiation therapy. We aimed to identify risk factors of local brain-progression after surgical metastases resection.
Methods: Two hundred thirteen patients operated on in a seven-year period with cerebral metastases of a carcinoma or melanoma, were retrospectively studied. Occurrence of local in-brain-progression was correlated with primary tumor entity, histopathological subtype, radiological features, adjuvant therapy and degree of surgical resection as assessed by an early post-operative MRI < 72h after surgery.
Results: 270 patients with 1-10 (BM) from NSCLC will be randomized in a ratio of 1:1 to receive stereotactic radio surgery (SRS) followed by either TTFields or supportive care alone. Patients are followed-up every two months until second cerebral progression. Patients in the control arm may cross over to receive TTFields at the time of progression. The objective of the METIS trial is to test the efficacy, safety and neurocognitive outcomes of TTFields in this patient population. Continuous TTFields at 150 kHz will be applied to the brain within 7 days of SRS. The treatment system is a portable medical device allowing normal daily life activities. Patients will receive the best standard of care for their systemic disease. The trial is designed to detect an increase in the time to cerebral progression from 7.7 to 13.4 months (hr 0.57) with 80% power at a 2-sided alpha of 0.05. The sample size was calculated using a log-rank with the competing risk taken as loss to follow up. Patients will be censored at time of death if it occurs prior to cerebral progression or neurological death. Primary endpoint is the time to cerebral progression, whereas the time to neurocognitive failure; overall survival; radiological response rate; quality of life; adverse events severity and frequency are secondary endpoints.
Summary: Antimitotic treatment with TTFields has shown efficacy in solid tumors, and needs to be evaluated in a prospective phase III trial in brain metastasis.
